Screening For Pulmonary Arterial Hypertension Research Articles

E061 Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: a survey of UK-based rheumatologists

Abstract Background/Aims Pulmonary arterial hypertension (PAH) affects approximately 10% of patients with SSc and is a major cause of morbidity and mortality. PAH is often asymptomatic, and therefore, proactive screening is crucial for early detection and improved survival, including through early treatment intervention. Although there are various proposed international guidelines for screening, there is currently no dedicated UK-based guidance. Our aim is to explore current UK screening practices for SSc-PAH patients, including identifying barriers and potential solutions. Methods A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment, and patient education. The survey was disseminated among rheumatologists working in the UK. Results Forty-four rheumatologists working in the UK participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised SSc units (university or general hospitals [54.5% and 45.4%, respectively]). The majority recognised that SSc-PAH is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for SSc-PAH, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to SSc-PAH screening (Figure 1A), with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions (Figure 1B). Conclusion Rheumatologists recognise that SSc-PAH screening is crucial to improve outcomes including survival; however, variable practices exist. There are various barriers to SSc-PAH screening and we have identified a number of practical potential solutions. Disclosure M.P. Álvarez Hernández: None. Y. Allanore: Honoraria; Speaking fees from Janssen outside the submitted work. I. Andrade: Other; Honoraria (speaker) fees, scientific board member for EchoRight™and advisory board participant for ‘Pulmonary hypertension in the primary care setting’ for Janssen, outside the submitted work. M.H. Buch: Other; Speaker fees from Boehringer Ingelheim, outside the submitted work. G. Coghlan: Other; Consultancy and working groups fees from Janssen and MSD; honoraria from Inari and Janssen; grants from Janssen. F. Del Galdo: Other; Consulting fees and research support from Janssen, outside the submitted work. C. Denton: Honoraria; Consulting fees and research support from Janssen, outside the submitted work. D. Khanna: Honoraria; Consultant: Amgen, Abbvie, BI, AZ, Merck, Horizon, Prometheus, Janssen, GSK. Grants- Pfizer, BI, Horizon. D.G. Kiely: Honoraria; Participation in advisory boards, steering committees, speaker fees and support to attend educational meetings from Acceleron, Gossamer, GSK, Janssen, Ferrer, MSD and United Therapeutics. Other; grant funding from GSK and Janssen. His work is supported by a grant from the NIHR Biomedical research Centre Sheffield. J. Pauling: Honoraria; Consultancy work for AstraZeneca, Boehringer Ingelheim, IsomAb, Janssen, Permeatus and Sojournix; speaker honoraria and educational support from Janssen. S. Ramjug: Consultancies; Consulting fees from Janssen, outside the submitted work. M. Hughes: Other; Speaking fees from Actelion, Eli Lilly, Janssen and Pfizer, outside the submitted work; research funding from Janssen; member of a data and safety monitoring board for Certa Therapeutics.

Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: A survey of UK-based rheumatologists.

The objectives were to explore rheumatologists' current clinical screening practices of pulmonary arterial hypertension in patients with systemic sclerosis in the United Kingdom and to identify barriers to screening and consider potential solutions. A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment and patient education. The survey was disseminated among rheumatologists working in the United Kingdom. Forty-four rheumatologists working in the United Kingdom participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised systemic sclerosis units (university or general hospitals (54.5% and 45.4%, respectively)). The majority recognised that systemic sclerosis-pulmonary arterial hypertension is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for systemic sclerosis-pulmonary arterial hypertension, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to systemic sclerosis-pulmonary arterial hypertension screening, with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions. Screening patients with systemic sclerosis for pulmonary arterial hypertension is crucial to improve survival, but variable practices exist among UK rheumatologists. Solutions include educating healthcare professionals on guidelines, sharing information between centres and integrating care services.

Impact of the COVID-19 Pandemic on Health Care Access and Diagnosis of Pulmonary Arterial Hypertension Among Patients With Systemic Sclerosis.

Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH. South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic. A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n=109), Victorian respondents (n=203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019. The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes.

Pulmonary vascular dysfunction in systemic sclerosis

PurposeThis study aimed to determine if any cases of pulmonary arterial hypertension (PAH) were missed using routine screening of systemic sclerosis (SSc). We assessed the potential benefits of adding the DETECT algorithm and invasive hemodynamic exercise testing into the local screening process in a Danish single-center cohort without known PAH. MethodsSeventy-three SSc patients (aged 60 ± 10 years; 56 (77%) females) underwent echocardiography. Among them, 24/73 had an elevated STEP 2 score of whom 3 had a high risk of pulmonary hypertension on echocardiographic assessment. Four patients declined right heart catheterization. Twenty patients (aged 62 ± 10 years, 13 (65%) females) underwent invasive haemodynamic assessment at rest. Nineteen patients participated in invasive haemodynamic exercise testing. ResultsAt rest, 3/20 patients met the 2022 ESC guidelines for PAH (mean pulmonary arterial pressure (mPAP) > 20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units). According to the 2015 ESC guidelines, only 1/19 patients had PAH. During exercise, 18/19 experienced a mPAP of > 30 mmHg, with the majority (13/19) showing an abnormal pulmonary pressure-flow relationship > 3 mmHg/L/min. Interestingly, seven out of nine patients with no pulmonary hypertension (PH) at rest had exercise-induced pulmonary hypertension. One-quarter of the patients had pulmonary hypertension associated with left ventricular dysfunction (Group 2 PH, WHO classification). ConclusionIn a Danish cohort of 73 SSc patients already undergoing bi-annual PAH screening, applying the DETECT algorithm identified three patients meeting the 2022 ESC/ERS guideline criteria for PAH at rest, one of whom demonstrated increased PAWP with exercise. However, many patients exhibited an abnormal pulmonary vascular response to exercise and/or signs of Group 2 PH.

Risk Factors for Pulmonary Arterial Hypertension in Patients With Systemic Lupus Erythematosus: A Systematic Review and Expert Consensus.

This study aimed to identify risk factors associated with the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE). We conducted a systematic literature review of studies focusing on adult patients classified as having SLE-related PAH by searching the electronic databases Embase, Medline, Medline in-progress, Wanfang, China National Knowledge Infrastructure, Ichushi Web, Kmbase, and KoreaMed. Based on the findings, we conducted a Delphi survey to build expert consensus on issues related to screening for PAH in patients with SLE and on the importance and feasibility of measuring the identified factors in clinical practice. We included 21 eligible studies for data synthesis. Sixteen factors were associated with an increased risk of SLE-PAH: pericardial effusion, serositis, longer duration of SLE, arthritis, acute and subacute cutaneous lupus, scleroderma pattern on nailfold capillaroscopy, diffusion capacity of carbon monoxide in the lungs (DLCO) <70% predicted, interstitial lung disease, thrombocytopenia, and seven serological factors. Six factors were associated with a decreased risk of SLE-PAH: malar/acute rash, hematologic disorder, renal disorder, higher Systemic Lupus Erythematosus Disease Activity Index score, and two serological factors. Among these, there were six risk factors on which the panelists reached strong or general consensus (peak tricuspid regurgitation velocity on echocardiography >2.8 m/s, pericardial effusion, DLCO <70% predicted, scleroderma pattern on nailfold capillaroscopy, brain natriuretic peptide >50 ng/l, and N-terminal pro-brain natriuretic peptide >300 ng/l). The Delphi panel confirmed the need for a screening tool to identify patients with SLE at high risk of developing PAH and provided consensus on the importance and/or practicality of measuring the identified factors. The risk factors we identified could be used in a screening algorithm to identify patients with SLE with a high risk of developing PAH to facilitate early diagnosis, which could improve prognosis and management of these patients.

Use of exercise tests in screening for pulmonary arterial hypertension in systemic sclerosis: A systematic literature review

Background and objective: Patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) have a poor prognosis, accounting for 30% of all SSc-related deaths. Guidelines recommend annual screening for PAH regardless of symptoms, as early treatment improves outcomes. Current protocols include combinations of clinical features, biomarkers, pulmonary function tests, and echocardiography. None include exercise testing, although early-stage PAH may only be evident during exercise. This systematic review assessed the performance of exercise tests in predicting the presence of PAH in patients with SSc, where PAH was confirmed through right heart catheterisation (RHC). Methods: Comprehensive literature searches were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trails, CINAHL, Scopus and Web of Science from inception to May 2023. Articles were screened for eligibility by two independent reviewers. Eligibility criteria included the use of a non-invasive exercise test to screen adult patients to detect PAH in a population without a previous diagnosis of PAH, with diagnosis confirmed by RHC. Results: Eight studies met the inclusion criteria, describing at least one of three different non-invasive exercise tests: cardiopulmonary exercise test, six-minute walk test and stress Doppler echocardiography. All studies found that exercise tests had some ability to predict the presence of PAH, with sensitivity between 50% and 100% and specificity from 73% to 91%. Conclusion: Exercise tests are infrequently used for screening for PAH in SSc but can predict the presence of PAH. More data are required to establish which tests are most effective.

Connective tissue disease‐associated pulmonary hypertension: A comprehensive review

AbstractConnective tissue diseases (CTDs) can be associated with various forms of pulmonary hypertension, including pulmonary arterial hypertension (PAH), pulmonary veno‐occlusive disease, pulmonary venous hypertension, interstitial lung disease‐associated pulmonary hypertension, chronic thromboembolic pulmonary hypertension, and sometimes a combination of several processes. The prevalence of PAH varies among the different CTDs, with systemic sclerosis (SSc) having the highest at 8%–12%. The most recent European Society of Cardiology/European Respiratory Society guidelines recommend routine annual screening for PAH in SSc and CTDs with SSc features. As CTDs can be associated with a myriad of presentations of pulmonary hypertension, a thorough evaluation to include a right heart catheterization to clearly delineate the hemodynamic profile is essential in developing an appropriate treatment plan. Treatment strategies will depend on the predominant phenotype of pulmonary vasculopathy. In general, management approach to CTD‐PAH mirrors that of idiopathic PAH. Despite this, outcomes of CTD‐PAH are inferior to those of idiopathic PAH, with those of SSc‐PAH being particularly poor. Reasons for this may include extrapulmonary manifestations of CTDs, including renal disease and gastrointestinal involvement, concurrent interstitial lung disease, and differences in the innate response of the right ventricle to increased pulmonary vascular resistance. Early referral for lung transplant evaluation of patients with CTD‐PAH, particularly SSc‐PAH, is recommended. It is hoped that in the near future, additional therapies may be added to the armamentarium of effective treatments for CTD‐PAH. Ultimately, a better understanding of the pathogenesis of CTD‐PAH will be required to develop targeted therapies for this morbid condition.

Screening for pulmonary arterial hypertension in patients with systemic sclerosis in the era of new pulmonary arterial hypertension definitions.

This study compares the performance of three composite pulmonary arterial hypertension (PAH) screening tools in a real-life SSc cohort, according to both the previous 2015 ESC/ERS guideline and the recent 2022 ESC/ERS guideline haemodynamic criteria. Consecutive SSc patients without a previous diagnosis of pulmonary hypertension (PH) were screened for PAH using the European Society of Cardiology/European Respiratory Society (ESC/ERS), DETECT, and Australian Scleroderma Interest Group (ASIG) algorithms. Right heart catheterisation (RHC) referral performances for PAH were compared according to the 2022 ESC/ERS PAH criteria. Thirty-five of the 81 patients required RHC; 15 (18.5%) according to ESC/ERS, 27 (33.3%) according to DETECT, and 25 (31%) according to ASIG. The final diagnoses were no-PH in 17 patients, WHO group 1 PH (PAH) in 8 patients, WHO group 2 PH in 8 patients, and WHO group 3 PH in 2 patients. When the hemodynamic criteria of the previous ESC/ERS guideline were applied, only one patient was diagnosed with PAH. The sensitivities of the algorithms for the diagnosis of PAH were 62.5% for ESC/ERS, 75% for DETECT, 87.5% for ASIG according to the 2022 ESC/ERS guideline definition, and 100% for all according to the previous ESC/ERS guideline. With the recent criteria, PAH diagnosis in patients with SSc increased by 1.8-fold. Current algorithms for screening PAH are less sensitive with these revised criteria. Although the ASIG algorithm seems more sensitive, it can still miss the diagnosis. The multimodal/algorithmic approach seems to be the best option for predicting PAH.

Defining minimal detectable difference in echocardiographic measures of right ventricular function in systemic sclerosis

BackgroundEchocardiography (2DE) is integral for screening and longitudinal evaluation of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). In the present study, we sought to establish the reliability, repeatability, and reproducibility of 2DE parameters in SSc patients with and without PAH and to define the minimal detectable difference (MDD), the smallest change detected beyond measurement error.MethodsSSc patients without known PAH and with invasively confirmed PAH on stable therapies underwent 2DE with strain at two time points. Analysis of variance (ANOVA) and coefficients of variation (CV) were calculated to assess for repeatability, reliability, and reproducibility. Intra- and inter-observer agreement were assessed using intraclass correlation. Bland-Altman analysis explored the level of agreement between evaluations. MDD was calculated using the standard error of measurement for each parameter by cohort.ResultsANOVA demonstrated few significant differences between evaluations across groups. Global right ventricular longitudinal systolic strain (GRVLSS, 9.7%) and fractional area change (FAC, 21.3%) had the largest CV, while tricuspid annular plane excursion (TAPSE), S’ wave, and right ventricular outflow track velocity time integral (RVOT VTI) were 0.87%, 3.2%, and 6.0%, respectively. Intra- and inter-observer agreement was excellent. MDD for TAPSE, FAC, S’ wave, RVOT VTI, GRVLSS, and RVSP were 0.11 cm, 0.03%, 1.27 cm/s, 0.81 cm, 1.14%, and 6.5 mmHg, respectively.ConclusionsWe demonstrate minimal measurement error in clinically important 2DE-based measures in SSc patients with and without PAH. Defining the MDD in this population has important implications for PAH screening, assessment of therapeutic response, and sample size calculations for future clinical trials.

Increased Levels of ICOS and ICOSL Are Associated to Pulmonary Arterial Hypertension in Patients Affected by Connective Tissue Diseases.

Background: Pulmonary hypertension (PH) is a life-threatening complication of connective tissue diseases (CTD); in this study, we aimed at investigating the potential role of inducible co-stimulator (ICOS) and its ligand (ICOS-L) as biomarkers of PH in CTD. Materials and Methods: We recruited 109 patients: 84 CTD patients, 13 patients with CTD complicated by pulmonary arterial hypertension (PAH), and 12 subjects with PAH alone. All recruited patients underwent a complete clinical and instrumental assessment along with quantitative measurement of serum ICOS and ICOS-L. Results: Independently of the underlying cause, patients with PAH were older and had a lower glomerular filtration rate. Interestingly, patients with both CTD-related and CTD-unrelated PAH had higher ICOS and ICOS-L serum concentrations than CTD patients (0.0001 for both). When compared to CTD patients, those affected by CTD-PAH showed higher ICOS (440 (240–600) vs. 170 (105–275) pg/mL, p = 0.0001) and ICOS-L serum concentrations (6000 (4300–7000) vs. 2450 (1500–4100) pg/mL; p = 0.0001). In a logistic regression, ICOS and ICOS-L were associated with a diagnosis of PAH, independently from age, gender, and renal function. The corresponding receiver operating characteristic (ROC) curves demonstrated a good diagnostic performance for both ICOS and ICOS-L. Conclusions: ICOS and ICOS-L are increased in patients with PAH, irrespectively from the underlying cause, and represent promising candidate biomarkers for the diagnostic screening for PAH among CTDs patients.

In systemic sclerosis TAPSE/sPAP ratio is correlated with ventilatory efficiency and exercise capacity assessed by CPET

ObjectivesThe aim of the study was to evaluate the correlation between cardiopulmonary exercise testing (CPET) parameters and right ventricular echocardiographic parameters for pulmonary arterial hypertension screening in a cohort of systemic sclerosis (SSc) patients. Methods forty SSc patients were examined using CPET and resting transthoracic echocardiography. CPET parameters analyzed were minute ventilation/carbon dioxide production (VE/VCO2) slope and maximum oxygen uptake (VO2 max); echocardiographic parameters were systolic pulmonary artery pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/sPAP ratio. Results a positive correlation was observed between VE/VCO2 slope and age (r = 0.415, p < 0.01) and sPAP (r = 0.461, p < 0.01), conversely, a negative correlation was found between VE/VCO2 slope and TASPE/sPAP ratio (r = − 0.521, p = 0.001). VO2 max showed an inverse correlation with age (r = − 0.367, p < 0.05) and sPAP (r = − 0.387, p < 0.05) and a positive correlation with TAPSE/sPAP ratio (r = 0.521, p < 0.01). On stepwise linear regression analysis, VE/VCO2 slope was significantly correlated with TAPSE/sPAP ratio (β coefficient = − 0.570; p < 0.0001), as well as VO2 max was significantly correlated with TAPSE/sPAP ratio (β coefficient = 0.518; p = 0.001). Conclusion in SSc patients, TAPSE/sPAP ratio is the echocardiographic parameter of RV function which showed the best correlation with ventilatory efficiency and exercise capacity.

Impact of routine screening on detection, severity and outcome of pulmonary arterial hypertension in systemic sclerosis

Abstract Introduction It has been reported that up to 20% of systemic sclerosis (SSc) patients can be asymptomatic at the time of pulmonary arterial hypertension (PAH) diagnosis. The significant prevalence rate, lack of symptoms and high morbidity and mortality from SSc-PAH as well as the potential benefit from early intervention with the more widely available therapeutic options provide a strong rationale for active screening programs. The DETECT algorithm was developed in 2013 from a large prospective and multicentre study in SSc patients with higher risk of PAH. The objective of this study was to examine the impact of a screening program on the early detection of SSc-PAH. We looked at serial patients diagnosed with SSc associated PAH (SSC-PAH) in a large national pulmonary hypertension referral centre. Patients and methods All newly diagnosed adult patients with SSc-PAH prospectively enrolled in a large national pulmonary hypertension referral centre. The current study included newly diagnosed patients between January 2006 and January 2018. Results Three-hundred and five patients were diagnosed with SSc-PAH in our centre between 2006 and 2018. Of these, 164 patients were diagnosed before 2013 (January 2006 - December 2012) and 141 after 2013 (January 2013 - January 2018). Demographics were similar at presentation between the two groups. The non-invasive (WHO-FC, 6-MWD and NT-proBNP) and haemodynamic measurements (RAP, CI and SvO2) were used to calculate the ESC guidelines risk score. It was noted that higher proportion of patients in the post-2013 were in the higher risk categories than the pre 213 group (84.4% vs. 78%) but this was not found to be statistically significant (p value 0.356). There was no statistically significant difference in survival between the two groups (Post 2013 group, 1-, 3- year and 5-year survival was 87.9%, 60.4% and 52.1%, respectively and pre-2013 group 1-, 3- year and 5-year survival 89.6%, 65.2% and 49%, respectively) with a log rank p value of 0.869. Applying Cox regression analysis of proportional hazard and adjusting for ESC risk score at baseline, predicted survival was not found to be statistically different between the two groups. The ESC risk category at baseline was a highly significant predictor of survival as expected. Conclusion There remains a strong rationale for active screening for PAH in SSc patients which has a poor prognosis despite advances in therapeutic strategies. However, the current screening programme does not seem to have resulted in significantly earlier detection in this cohort. It would be important to analyse other patient populations in order to understand the impact of screening programmes. The current screening programs limitations may explain why we have not been able to detect more patients in the lower risk categories. Further development of these programs in order to overcome their shortfalls is direly needed. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Health ServiceRoyal Free NHS Trust Survival analysis

In systemic sclerosis, the TAPSE/sPAP ratio can be used in addition to the DETECT algorithm for pulmonary arterial hypertension diagnosis.

Early detection of pulmonary arterial hypertension (PAH) is crucial for improving patient outcomes. The aim of this study was to compare the positive predictive value (PPV) of the echocardiography-derived tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with that of the DETECT algorithm for PAH screening in a cohort of SSc patients. Fifty-one SSc patients were screened for PAH using the DETECT algorithm and echocardiography. Echocardiography was recommended by the DETECT algorithm step 1 in 34 patients (66.7%). Right heart catheterization (RHC) was recommended by the DETECT algorithm step 2 in 16 patients (31.4%). PAH was confirmed by RHC in 5 patients. The DETECT algorithm PPV was 31.3%. The TAPSE/sPAP ratio was higher in SSc patients not referred for RHC than in SSc patients referred for RHC according to the DETECT algorithm step 2 [0.83 (0.35-1.40) mm/mmHg vs 0.74 (0.12-1.09) mm/mmHg, P < 0.05]. Using a cut-off of 0.60 mm/mmHg, 8 (15.7%) SSc patients had a TAPSE/sPAP ratio of ≤0.60 mm/mmHg. PAH was confirmed by RHC in 5 patients. The PPV of TAPSE/sPAP was 62.5%. In multiple regression analysis, TAPSE/sPAP was associated with age [β coefficient = -0.348 (95% CI: -0.011, -0.003); P < 0.01], DETECT algorithm step 1 [β coefficient = 1.023 (95% CI: 0.006, 0.024); P < 0.01] and DETECT algorithm step 2 (β coefficient = -1.758 [95% CI: -0.059, -0.021]; P < 0.0001). In SSc patients with a DETECT algorithm step 2 total score of >35, the TAPSE/sPAP ratio can be used to further select patients requiring RHC to confirm PAH diagnosis.

Pulmonary Arterial Hypertension in Indonesia: Current Status and Local Application of International Guidelines.

Recent advances in the diagnosis and management of pulmonary arterial hypertension (PAH) have led to a significant improvement in the outcomes for patients with PAH. However, prompt and accurate diagnosis of PAH remains an unmet challenge due to lack of awareness and lack of meticulous data to profile the etiology and pathophysiology of this rare progressive disease, especially in low- and middle-income country. In Indonesia, the true prevalence and incidence of different subtypes of PAH in general population is still unknown. The Congenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry was the first single-center prospective registry in Indonesia, which indicated that almost 80% of adult patients with congenital heart disease (CHD) had experienced PAH and even Eisenmenger syndrome due to delayed diagnosis. Screening for early detection of asymptomatic CHD in children is yet to be systematically established in Indonesia, leading to undiagnosed and uncorrected CHD in adulthood. There are no specific national guidelines focusing on diagnostic workup and treatment of PAH in Indonesia. Furthermore, the lack of adequate diagnostic facilities, limited treatment availability, and limited drug coverage under the National Health Insurance Scheme are key issues that remain unaddressed. This review focuses on the diagnosis, treatment, and management of PAH associated with CHD in Indonesia as per international guidelines. We have proposed recommendations to effectively control and prevent PAH associated with CHD in Indonesia. The paper should be of interest to readers in the area of medical management and policy makers especially in low- and middle-income countries.Key Highlights:Pulmonary arterial hypertension (PAH) is a rare progressive subtype of pulmonary hypertension with poor overall prognosis and outcomes.Prompt and accurate diagnosis of PAH remains an unmet challenge in low- and middle-income countries due to poor knowledge about the etiology and pathophysiology of this syndrome. Also, the symptoms and signs of early-stage PAH are usually nonspecific or undetectable in newborn and infants, thus presenting a challenge for physicians to establish early diagnoses of PAH.The challenging factors in low- and middle-income countries, especially Indonesia archipelago are limitations of healthcare infrastructure, limited expertise, lack of awareness, lack of timely PAH screening strategies, poor antenatal care and unpredictable availability of PAH medications.There are no specific national guidelines focusing on diagnostic workup and treatment of PAH in Indonesia. Under-utilization of treatment guidelines and lack of adequate diagnostic treatment facilities have resulted in sub-optimal management of PAH patients in Indonesia.Adherence to international guidelines is an important aspect of PAH management in Indonesia. Updated disease and functional classifications of PAH as per international guidelines along with new research findings on prognostic factors can help in making better management decisions for PAH patients at different stages of the disease.

Screening for the early detection of pulmonary arterial hypertension in patients with systemic sclerosis: A systematic review and meta-analysis of long-term outcomes

BackgroundSystemic sclerosis (scleroderma, SSc) is a chronic multisystem autoimmune disease characterised by fibrosis of the skin and internal organs and vasculopathy. One of the major contributors to mortality in patients with SSc is pulmonary arterial hypertension (PAH). International recommendations advise annual screening for the early detection of PAH in asymptomatic patients with SSc. ObjectivesTo evaluate by systematic review current measures employed for screening for PAH. To summarise by meta-analysis the current evidence for long-term outcomes of screening for PAH in SSc. MethodsManuscripts published until 12th March 2019 were identified through searching Medline, Embase and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Eligible studies included abstracts or full reports investigating patients with SSc undergoing screening by any protocol to detect PAH. Risk of bias was assessed with reference to the QUADAS-2 tool. ResultsThe review resulted in 580 unique citations with 15 manuscripts included for final systematic review of screening methods, and six for meta-analysis. The systematic review demonstrated that there are varying protocols for screening for PAH. Screened populations were reported to have better risk stratification parameters at PAH diagnosis. Meta-analysis showed improved survival in patients with SSc-PAH diagnosed as a result of screening. There were trends towards having better risk stratification parameters at PAH diagnosis in those screened, although not all of these were statistically significant. LimitationsThere are no randomised controlled trials of screening for PAH in patients with SSc and the evidence presented in this review is derived from publications of registry data, cross-sectional and cohort studies. ConclusionsThis review demonstrates long-term benefit through the systematic screening of patients with SSc of varying disease duration for the early detection of PAH. Screened cohorts had improved survival, and were more likely to have better prognostic factors at the time of diagnosis with PAH.

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

BackgroundHeritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population.MethodsAsymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline.Results55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up.ConclusionsAsymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.

Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK).Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity).This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.

Screening for pulmonary arterial hypertension in systemic sclerosis: Now or never!

Systemic sclerosis (SSc), a chronic multisystem autoimmune disease characterized by fibrosis of the skin and internal organs and vasculopathy, has a high burden of mortality. One of the major contributors to mortality in patients with SSc is pulmonary arterial hypertension (PAH), which affects up to 10% of individuals and results in up to 15 years of life loss. Best practice recommendations are for asymptomatic patients with SSc and SSc-spectrum disorder to be screened annually for the early detection of SSc-PAH. Recently published data from large registries have shown improvements in the long-term outcomes in patients who are diagnosed with SSc-PAH because of systematic annual screening. This review will address the current clinical and research implications of the screening for the early detection of SSc-PAH.

Pulmonary arterial hypertension screening practices in scleroderma patients among Canadian rheumatologists.

Current international guidelines recommend annual screening for pulmonary arterial hypertension with transthoracic echocardiogram and pulmonary function testing in all patients with scleroderma (systemic sclerosis). Our objectives were to determine Canadian rheumatologists' screening practices for pulmonary arterial hypertension in patients with systemic sclerosis and identify reasons why current guideline recommendations may not be followed. A survey was emailed to all Canadian Rheumatology Association members. They self-identified as systemic sclerosis experts or non-experts and provided basic demographic data. Participants were asked how frequently they screened with transthoracic echocardiogram and pulmonary function testing and, if applicable, why they did not adhere to recommendations. A total of 71 rheumatologists participated, of whom 43 identified as non-experts. Overall, 81.4% ordered annual transthoracic echocardiogram and 77.6% annual pulmonary function testing. Rates of annual transthoracic echocardiogram testing were similar between experts and non-experts, whereas experts ordered annual pulmonary function testing more often. Clinicians with a higher proportion of systemic sclerosis patients in their practice were more likely to follow guidelines. There was an inverse relationship between years in practice and adherence to screening guidelines. The most common reason for not following screening guidelines was disagreement with recommendations, followed by unfamiliarity with guidelines. Pulmonary arterial hypertension screening rates remain sub-optimal in Canada but have improved since 2012. Failure to adopt guidelines is due to rheumatologists disagreeing with or not knowing current recommendations. Future studies should examine why rheumatologists disagree with guidelines and how to improve awareness.

Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China.

Primary Sjögren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH. We established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation. The case-control study was conducted with pSS-non-PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits. In total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non-PAH patients as controls. The presence of anti-SSB (p<0.001, OR 4.095) and anti-U1RNP antibodies (p<0.001, OR 29.518), the age of pSS onset (p<0.001, OR 0.651) and the positivity of corneal staining (p=0.003, OR 0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, hazard ratio (HR) 0.161), pulmonary vascular resistance (p=0.016, HR 1.105) and Sjögren's syndrome disease damage index (p=0.006, HR 1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p<0.0001). The routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patient prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.